The long-term goal of this research is to identify the specific mechanisms involved in severely disturbed interpersonal relationships that exemplify Borderline Personality Disorder (BPD). Part of this long-term goal is the aim to identify mechanisms using a translational research approach that utilizes several different levels of analysis: neural, physiological, behavioral and phenomenological. The proposed research is specifically aimed at identifying the characteristic patterns of electrophysiological, behavioral and phenomenological reactions to interpersonal rejection in individuals with BPD in contrast to two control groups: individuals with major depression and healthy controls. DSM-IV Axis I and II disorders will be assessed amongst all participants prior to participation in two studies of social rejection. In the first, a startle probe paradigm will be used to assess the threatening nature of rejection related paintings in contrast to paintings depicting acceptance or positive, negative and neutral themes. Startle response will be assessed by electromyography recorded from electrodes just below the left eye. When viewing stimuli that are particularly aversive or threatening to an individual, startle response tends to be elevated, thought to reflect the activation of a defensive motivational system. In the second study, focused on reactions to interpersonal stress, participants will play a computerized ball-toss game which has been validated as an effective manipulation to induce the experience of social rejection. EEG asymmetry will be assessed before, during and after the game. Participants will complete self-report measures of anger, perception of other players, and complete a task measuring behavioral aggression. It is predicted that both BPD and MDD participants will demonstrate elevated startle response to rejection themed paintings, but will show several differences in reactions to social rejection: 1) BPD patients will show greater relative left frontal activation, and 2) will demonstrate greater behavioral aggression and more malevolent perceptions of other "players". The proposed research is important to public health because the disorder is highly prevalent and poses a severe mental health burden. In addition disturbed interpersonal relatedness is a prominent and specific feature of BPD, is highly debilitating, and yet poorly understood. For individuals with BPD, subtle, benign interpersonal events can evoke intense emotional responses, angry outbursts and maladaptive, life threatening behaviors. Uncovering the neural, physiological and behavioral processes that underlie disturbed relatedness in BPD is essential for informing the development of psychotherapy and pharmacotherapy and reducing mental health burden. PUBLIC HEALTH RELEVANCE: Borderline Personality Disorder is a severe mental health disorder characterized by intense negative emotion, anger, aggression, disturbed interpersonal relationships, maladaptive responses to real or perceived abandonment and self-harm and suicidal behaviors. Because real or perceived events in interpersonal relationships are linked to many prominent features of BPD, including aggressive acts, self-harm and suicidality, it is important to understand the nature of this disturbance. Identification of the nature of disturbance in interpersonal relationships can help lead to therapies that can lessen the severe pain and distress of the disorder, and lead to significantly improved functioning in the realms of work and relationships, lessening the costs of the disorder to the individual with BPD and the public.